DESCRIPTION [Provided by Applicant): The overarching goal of this application is to link social-affective functions to their underlying neurobiological and molecular genetic bases, using Williams syndrome (WS) as a model. The theme leads from the investigators' past studies to the hypothesis that genetic and neuropeptide dysregulation underlies the social-affective features of WS. They continue to employ a multi-pronged approach incorporating new techniques and approaches to understanding the neurogenetic systems involved in the WS social phenotype. To this end, Project I: Gene Networks for Social Cognition, will determine the role of WS genes in social-emotional behavior using individuals with both full and atypical deletions; the role of genetic variations for neurotransmitters and neuropeptides in WS social-emotional behavior; the expression of WS and neuropeptide receptor genes in WS brain; and the genetic transcriptional networks altered in WS. Project II: Modeling WS using Human Neurons, will model typical and affected human nervous system development in WS using pluripotent stem cells. Studies will target genes implicated in social behavior within the WS region. Project III: Cellular Architectonics and Local Circuits, will examine the structures implicated in the social brain in WS on a unique collection of WS brains. Project IV: Neuroimaging of Social Circuitry, will utilize new multimodal, integrated structural and functional neuroimaging techniques to test hypotheses about the relationships among brain anatomy, physiology, cognition, and genetics in WS. Project V: Characterization of the Social Phenotype of WS, will characterize three independent key dimensions of altered social-affective behavior WS, including the pathways of several dissociations, incorporating new technologies and probes for behavior, psychophysiology, and electrophysiology. Genetic concepts have been used to map out the program project, and will be integrated at the level of the organism (Projects IV and V), brain/gene expression (Project III), and cell (Project II), to parse genes and transcriptional networks underlying social behavior. Results have the potential to move our understanding forward in unprecedented ways, providing a critical contribution to Social Neuroscience. RELEVANCE: A mission of NICHD includes research that leads to increased understanding and treatment of social behavior and emotional disorders. The investigators propose research that targets the study of genes, neural circuits, and social behavior in new and innovative ways, the results of the studies will provide unprecedented integration of the genetic and brain processes responsible for human social behavior, and key to novel treatments.